Apomorphine for patients with disorders of consciousness
“Taking care of patients in non-responsive wakefulness, minimally conscious or locked-in syndrome”
A project supported by the Fund Generet – King Baudouin Foundation
The study (ClinicalTrials.gov Identifier: NCT03623828 / EudraCT Identifier 2018-003144-23) investigates the effects of subcutaneously administered apomorphine in brain-injured patients with disorders of consciousness (DOC).
Apomorphine, a dopaminergic agent, has exhibited promising clinical effects in preliminary studies. However, the true efficacy and neural mechanisms of this drug for restoration of consciousness are unknown. This study is designed to confirm previously observed positive clinical responses in these patients (Fridman et al. 2009 & Fridman et al. 2010) and to correlate behavioral improvements with multimodal neuroimaging techniques.
Based on the mesocircuit model (Schiff 2010), this project aims to:
- Determine the efficacy of apomorphine to treat patients with DOC,
- Understand the mechanistic brain processes underlying the effect on consciousness recovery using advanced model-based imaging technology,
- Develop biomarkers predicting responsiveness to treatment,
- Evaluate treatment tolerance and side effects.
Forty-eight DOC patients will be randomized to receive a 30-day regimen of apomorphine or placebo. They will be monitored 30 days before therapy, during treatment and 30 days after treatment, using standardized clinical scales and brain-imaging techniques. Follow-up will be performed up to 2 years after treatment.
This will be the first study to investigate the use of apomorphine for the recovery of consciousness using multimodal assessments and response modeling in a randomized clinical trial (RCT).
Results should help to define clearer guidelines in the treatment of patients with disorders of consciousness and allow a better understanding of how dopamine networks are involved in consciousness and its impairments.
Pilot study is now successfully completed and RCT started in June 2021!
Article – 2021
“Repurposing apomorphine for chronic disorders of consciousness: a multimodal open-label study after apomorphine treatment for chronic disorders of consciousness: preliminary results”
LRD. Sanz, N. Lejeune, E. Szymkowicz, E. Bonin, R. Panda, A. Sala, A. Thibaut, D. Dikenstein, S. Van Goethem, D. Ledoux, N. Farber, J. Stender, RD. Zafonte, ND. Schiff, S. Laureys, O. Gosseries.